IndraLab

Statements


USP8 deubiquitinates SMO. 13 / 14
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"USP8 and UCHL5 deubiquitinases have been characterized to downregulate Smo ubiquitination."

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"Inactivation of the ubiquitin activating enzyme-Uba1 promotes Smo accumulation on the cell surface and Hh signaling activation, and USP8 decreases Smo ubiquitination to promote its cell surface accumulation in the absence or presence of Hh."

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"The catalytic domain of USP8 (USP8NT3) was sufficient to reduce Smo ubiquitination (XREF_FIG, lane 4, top panel), enhance the accumulation of endogenous Smo (XREF_FIG), and increase the GFP-Smo-mediated induction of ectopic dpp-lacZ and ptc expression (XREF_FIG, XREF_SUPPLEMENTARY '' ')."

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"USP8 prevents SMO ubiquitylation and increases HH signaling activity by promoting SHH-induced cell surface accumulation of SMO (205, 242), whereas USP48 interacts with GLI1 in the nucleus and thereby protects GLI1 from proteasome-dependent degradation."

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"Hh promotes the formation of a Smo and USP8 complex, and USP8 further promotes the accumulation of Smo at the cell surface and prevents localization to the early endosomes by deubiquitinating Smo, leading to increased Hh signaling activity."

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"SMO is deubiquitinated by USP8 and this modification alters its target region, possibly linking this mutation to the already described mechanisms of USP8-mutated adenomas [29]."

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"However, we found that UBPY decreases Smo ubiquitination regardless of the Hh signaling states and that the association between UBPY and Smo is not significantly affected by either Hh stimulation or Smo phosphorylation, suggesting that Smo deubiquitination by UBPY is unlikely to be a major mechanism by which Hh inhibits Smo ubiquitination, although we can not rule out the possibility that Hh regulates UBPY binding to Smo in a subtle way that escaped the detection by our coimmunoprecipitation assay."

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"Although our observations support the notion that USP8 deubiquitinates Smo and prevents localization to early endosomes, we are not suggesting that USP8 play an exclusive role in the inhibition of Smo endocytosis."

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"In addition, it has been reported that the deubiquitinase Usp8 could deubiquitinate Smo to influence Hh signaling activity."

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"Taken together, these results suggest that UBPY can reverse Smo ubiquitination to promote its cell surface accumulation and induce low but not high levels of Hh pathway activation."

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"As shown in XREF_FIG, USP8, but not the other DUBs, reduced the ubiquitination of Myc-Smo."

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"USP8 deubiquitinates HIF1a to control ciliogenesis in normoxia (Troilo et al., 2014) and antagonizes Smo ubiquitination (Ma et al., 2016)."

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"In addition, we provide evidence that the non visual beta-arrestin Krz acts in parallel with Smo ubiquitination to promote its internalization and that Smo ubiquitination is antagonized by the deubiquitinating enzyme UBPY."